Drugs for gout are used to reduce the pain and inflammation of acute flares, decrease the frequency of exacerbations, and lower serum urate levels to prevent recurrent flares, development of tophi, and joint damage.

View the Comparison Table: Some Drugs for Gout

Nonopioid drugs can be used in the treatment of many nociceptive and neuropathic pain conditions. For severe pain, especially severe chronic cancer pain, use of opioids may be necessary. Noninvasive nonpharmacologic treatments, including physical and psychological therapies, have been shown to improve pain and function in patients with some common chronic pain conditions and are unlikely to cause serious harms. A multimodal approach to analgesic therapy can increase pain control while reducing opioid use and adverse effects.

Many different drugs are used for treatment of osteoarthritis pain, but none of them prevent progression of the disease. Nonpharmacologic approaches including weight management, exercise, tai chi, physical therapy, assistive devices, and total joint arthroplasty can also be used. The American College of Rheumatology (ACR) has published new guidelines for the management of osteoarthritis of the hip, hand, and knee.

Drugs for gout reduce the pain and inflammation of acute flares and lower serum urate levels in order to prevent recurrent flares, development of tophi, and joint damage.

Nonopioid drugs can be used in the treatment of many nociceptive and neuropathic pain conditions. Use of opioids for pain will be reviewed in a future issue.

The FDA has approved Vivlodex (Iroko), a low-dose formulation of the nonsteroidal anti-inflammatory drug meloxicam (Mobic, and generics), for management of osteoarthritis pain. According to the manufacturer, the new formulation aligns with stronger FDA warnings about the cardiovascular risks of NSAIDs and the recommendation to use the lowest possible doses of these drugs.

The same pharmaceutical company (Iroko) that recently marketed low-dose diclofenac (Zorvolex) for treatment of mild to moderate acute pain1 has now received approval from the FDA to market a low-dose oral formulation of indomethacin (Tivorbex) for the same indication. Tivorbex is available in 20- and 40-mg capsules; conventional immediate-release indomethacin capsules contain 25 mg and 50 mg of the drug.

The rationale for this new product is the same as the one offered for Zorvolex: the drug is formulated as submicron particles that increase surface area, leading to faster dissolution and absorption. According to the package insert, the time to reach peak serum concentrations (Tmax) was 1.67 hours with a 40-mg capsule of Tivorbex, compared to 2.02 hours with a standard 50-mg capsule of indomethacin.

The problem with Tivorbex is the same as the problem with Zorvolex: there are no studies comparing its efficacy to that of standard doses of indomethacin or to any other NSAID. In addition, indomethacin is generally considered one of the most potent NSAIDs and one of those most likely to cause GI bleeding, increase cardiovascular risk, and damage the kidneys. There is no good reason to use indomethacin in any dosage for treatment of mild to moderate pain.

1. Low-dose diclofenac (Zorvolex) for pain. Med Lett Drugs Ther 2014; 56:19.

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The goals of gout treatment are threefold: treating acute inflammation, preventing flares, and lowering serum urate levels.

Disease-modifying anti-rheumatic drugs (DMARDs) are now used early in the treatment of rheumatoid arthritis (RA) to achieve clinical remission, prevent irreversible damage to joints, and minimize toxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. DMARDs (Table 1) generally do not have an immediate analgesic effect, but over time can control symptoms and have been shown to delay and possibly stop progression of the disease. NSAIDs have immediate analgesic and antiinflammatory effects, but may not affect the disease process. Oral corticosteroids can relieve joint symptoms and control systemic manifestations, but their chronic use can cause many complications. Judicious use of intra-articular corticosteroids can rapidly decrease inflammation in acute joints with few, if any, adverse effects.

Until the recent introduction of febuxostat (Uloric), no new drugs had been marketed for treatment of gout in the past 40 years. Colchicine, which has been available for decades as an unapproved drug, has now been approved by the FDA (Colcrys) for treatment and prophylaxis of gout flares. It was approved earlier only in combination with probenecid (Colbenemid, and others). The goals of gout treatment are three-fold: treating acute disease, preventing flares and reducing uric acid stores.

Disease-modifying anti-rheumatic drugs (DMARDs) are now used early in the treatment of rheumatoid arthritis (RA) to prevent irreversible damage to joints and minimize toxicities associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids.

The FDA recently advised health care professionals and consumers not to use a number of dietary supplements found to contain the phosphodiesterase-5 inhibitor sildenafil (Viagra) or an analog of the drug (www.fda.gov). Although the effects of sildenafil may be noticeable (in men), the presence of other, possibly more toxic adulterants in dietary supplements may be more difficult or impossible to detect.

Other drugs previously found in dietary supplements have included lovastatin (Mevacor, and others), estrogen, alprazolam (Xanax, and others), indomethacin (Indocin, and others) and warfarin (Coumadin, and others). Aristolochic acid in Chinese herbal weight loss products caused acute renal failure in about 100 women in Belgium; at least 70 of them required dialysis or transplantation, and at least 18 developed urothelial cancer (Med Lett Drugs Ther 2002; 44:84).

Dietary supplements do not require FDA approval before marketing. The agency does have the power to remove mislabeled or adulterated products from store shelves, but the burden of discovery and proof is entirely on the government.

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To prevent irreversible damage to joints and minimize toxicities associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, disease modifying anti-rheumatic drugs (DMARDs) are now used early in the treatment of rheumatoid arthritis (RA). The DMARDs listed in the table on page 84 have no immediate analgesic effects, but can control symptoms and have been shown to delay and possibly stop progression of the disease. The NSAIDs listed in the table on page 88 have analgesic and anti-inflammatory effects, but may not affect the disease process. Oral corticosteroids can rapidly relieve joint symptoms and control systemic manifestations, but their chronic use is associated with many complications.

Three types of analgesic drugs are available: non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; opioids; and adjuvant drugs that are not usually thought of as analgesics, such as antidepressants, which can act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Combining two different types of analgesics may provide an additive analgesic effect without necessarily increasing adverse effects.

Many different drugs are now used to treat rheumatoid arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs), listed in the table on page 26, have analgesic and anti-inflammatory effects, but may not affect the disease process. Corticosteroids can provide rapid relief of joint symptoms and control of systemic manifestations, but chronic use is associated with many complications. The "disease-modifying" anti-rheumatic drugs (DMARDs), listed on page 29, have no immediate analgesic effects, but can control symptoms and may delay progression of the disease (American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines, Arthritis Rheum 2002; 46:328). Interactions of anti-rheumatic drugs with other drugs are listed in The Medical Letter Handbook of Adverse Drug Interactions, 2003.

Since the last Medical Letter article on glucosamine for osteoarthritis (vol.39, page 91, September 26, 1997), more data have become available. Glucosamine is available in US pharmacies and health food stores as sulfate, hydrochloride or n-acetyl salt.

Many different drugs are now used to treat rheumatoid arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic and anti-inflammatory effects, but may not affect the disease process. The "disease-modifying anti-rheumatic"drugs (DMARDs) have no immediate analgesic effects, but can control symptoms and may delay progression of the disease.

Spironolactone, an aldosterone receptor antagonist, has been FDA-approved for many years for treatment of edema, hypertension and primary hyperaldosteronism. Recently, it was reported to improve morbidity and mortality in patients with severe heart failure.

Oxaprozin (Daypro -Searle), a propionic acid-derivative nonsteroidal anti-inflammatory drug (NSAID), has been approved by the US Food and Drug Administration for once-daily treatment of rheumatoid arthritis and osteoarthritis. Some of the NSAIDs previously marketed in the USA are listed in the table on page 16. Ibuprofen, naproxen, fenoprofen, ketoprofen, and flurbiprofen are also propionic acid derivatives. Piroxicam and nabumetone (Medical Letter, 34:38, 1992) are also approved for once-daily use, and indomethacin is available in an extended-release formulation that can be taken once a day.

Nabumetone (Relafen - SmithKline Beecham), a new nonsteroidal anti-inflammatory drug (NSAID), has been approved by the US Food and Drug Administration for treatment of rheumatoid arthritis and osteoarthritis. The drug has been available in the United Kingdom since 1987. The manufacturer claims that nabumetone is as effective as other NSAIDs and causes a relatively low incidence of peptic ulcers.

Etodolac (Lodine - Wyeth-Ayerst), a nonsteroidal anti-inflammatory drug (NSAID) available in Europe for several years, was recently approved by the U.S. Food and Drug Administration for use in osteoarthritis and as a general-purpose analgesic. It has not been approved for treatment of rheumatoid arthritis.

Some commonly used systemic drugs that may cause pulmonary toxicity are listed in the table below. These adverse effects may sometimes be difficult to distinguish from the underlying disease (JAD Cooper, Jr et al, Am Rev Respir Dis, 133:321, 488, 1986). Pulmonary effects that are part of a generalized reaction or are indirect effects of drugs - on respiratory muscles, for example, or on the immune system - are not included here.

Ketorolac (kee'; toe role ak) tromethamine (Toradol), manufactured by Syntex but also marketed by Roche, is the first parenteral nonsteroidal anti-inflammatory drug (NSAID) to become available for analgesic use in the USA. Parenteral indomethacin (Indocin I.V.) has been marketed here since 1985, but only for treatment of patent ductus arteriosus in newborn infants. Other parenteral NSAIDs are available in other parts of the world, but low potency, poor aqueous solubility, and substantial tissue irritation on injection have limited their usefulness. Ketorolac has been approved by the US Food and Drug Administration for intramuscular (IM) treatment of moderate to severe pain.

Flurbiprofen (Ansaid - Upjohn), a nonsteroidal anti-inflammatory drug (NSAID) available in some countries since 1977, was recently approved by the US Food and Drug Administration for treatment of rheumatoid arthritis and osteoarthritis. Flurbiprofen is a fluorinated phenylalkanoic acid derivative structurally related to ibuprofen (Motrin;and others).

Diclofenac sodium (Voltaren - Geigy), a nonsteroidal anti-inflammatory drug (NSAID) available in some countries since 1974, was recently introduced in the USA for treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. It is being promoted as 'The number one prescribed antiarthritic in the world.'